The ultimate objective of the proposed research is to develop a photochemical method for the localized delivery of pharmaceutical agents in the mammalian body. Liposomes (microscopic bilayer phospholipid vesicles) have been used successfully to entrap drugs for intravenous injection. If photodynamic sensitizers are incorporated into liposomes, illumination increases the membrane permeability so that entrapped materials leak out. Injected photosensitive liposomes should deliver their contents more efficiently in localized areas of an organism exposed to high intensity light. The technique would be restricted to those parts of the body which can be illuminated including the skin, eye, and, with appropriate illuminators, the mouth, throat, external ear canal, vagina, etc. The proposed program is divided into three phases. The first is a detailed study of the preparation of highly photosensitive liposomes. In particular, the efficiencies of different kinds of sensitizing dyes, the effects of dye location within the liposome structure, and the molecular photochemistry of the reactions leading to increased membrane permeability will be examined using liposomes of different chemical composition and sizes. In the second phase, a study will be made of light induced drug release from photosensitive liposomes in cultures of mammalian cells; possible changes in the interactions of the liposomes with cell surfaces on illumination will also be examined. The third phase will involve a determination of the feasibility of obtaining the release of therapeutically useful amounts of drugs from photosensitive liposomes in localized illuminated regions of mice. In a sense, this approach represents a new type of sensitized photochemotherapy.